After years of research on genetic mutations of cells and a key discovery made of cells carrying KRAS gene mutations having large amounts of a reactive form of iron, scientists can attack this aspect of the mutated cells by delivering cancer medications to the “ferroaddicted” cells without causing damage to the healthy cells. This approach could spare cancer patients a significant level of discomfort going forward.
This has been done by taking the cancer drug Cobimetinib and adapting the medication to send ferrous iron-activatable drug conjugate (FeADC) to only the cells in the body with high iron concentrations.
“In this study, we describe a therapeutic strategy that enables more tolerable and efficacious combination therapies targeting the signaling pathways in KRAS-driven tumors,” said Eric Collisson, MD, a member of the University of California in San Fransisco (UCSF) Helen Diller Family Comprehensive Cancer Center. “The discovery of pharmacologically exploitable ferroaddiction in KRAS-driven cancers holds promise to improve the treatment of deadly cancers through a practicable and generalizable approach to FeADC design, development, and clinical testing.” This was quoted from Genetic Engineering & Biotechnology News.
Collisson was an author of the team’s publication in the Journal of Experimental Medicine (JEM) titled “Ferrous iron–activatable drug conjugate achieves potent MAPK blockade in KRAS-driven tumors.” The report goes into detail on the manipulation of iron in the study. “Ferrous iron accumulation is an exploitable feature of KRAS transformation, and FeADCs hold promise for improving the treatment of KRAS-driven solid tumors.”
KRAS mutations are one of the main members of the RAS gene family, they’re present in approximately 25% of tumors, making them one of the most common gene mutations linked to cancer. “They are frequent drivers in lung, colorectal and pancreatic cancers. In healthy cells, KRAS serves as an on-off switch that regulates cell growth. It does this by binding a KRAS-activating molecule called GTP and then converts it to GDP, which inactivates the protein. However, when the gene is mutated, KRAS can become stuck in the ‘on’ position, allowing cells to grow uncontrollably and activating the downstream pathways. This leads to multiplication of cells and cancer growth,” explains a study was done at the University of Texas.
“RAS proteins are important for normal development. Active RAS drives the growth, proliferation, and migration of cells. In normal cells, RAS receives signals and obeys those signals to rapidly switch between the active form and the inactive states. Mutated RAS* is stuck in the active state, ignores signals to the contrary, and drives cells to become cancerous,” explains Jim Hartley of the National Cancer Institute’s RAS Initiative.
Many of the medications available for the treatment of cancers cause adverse side effects and extreme discomfort for the suffering patients. By taking medications that were already approved by the FDA for treating cancers, scientists have been able to create something that will be able to attack cancer cells while leaving healthy cells intact. “This innovation allowed sustainable, effective treatment of tumor-bearing animals, with tumor-selective drug activation, producing superior systemic tolerability. Ferrous iron accumulation is an exploitable feature of KRAS transformation, the publication in JEM.